Summary of Work: The DFNB7 locus was initially mapped in two families from India. These two families made it possible to localize the gene within a 4 cM region of chromosome 9q11-q21. This region is syntenic to mouse chromosome 19 to which the deafness (dn) locus was mapped by Dr. Bronya Keats, LSU Medical Center, New Orleans LA. We have constructed a BAC contig through one of the dn chromosomal inversion breakpoints and sample sequencing has been performed in an effort to localize candidate cDNA molecules in the region of interest. Candidate genes will be tested against DNA from the dn mouse isolated in the laboratory of Dr. Steel. In 1993, four families in India were identified as being suitable for linkage analysis. Each family consisted of at least four affected children related to each other through a consanguineous union. Two families mapped to DFNB3; one family provided information for localization of the DFNB7 locus; and the fourth family is linked to a new locus, DFNB18. The information for the DFNB18 locus will be submitted for publication in the near future. Several additional Indian families have recently been identified which support LOD scores over 3 with nonsyndromic hereditary hearing impairment. DNA samples from these families are being analyzed for localization to known loci. Any families unlinked to the known loci will then be mapped to find additional locations for recessive loci causing nonsyndromic hereditary hearing impairment. The Center for Excellence in Molecular Biology in Pakistan has identified two very large consanguineous families with nonsyndromic hereditary hearing impairment. DNA from these families will also be collected and studied. There are multiple families in a small region of Newfoundland which have a high proportion of deaf children. Efforts are being made to collect appropriate phenotype data on these families. Most of the DNA samples from the area have been received. Mapping efforts in these families are inconclusive to date.